Since gene expression approaches constitute a starting point for investigating plant–pathogen systems, we performed a transcriptional analysis to identify a set of genes of interest in tomato plants infected with F. oxysporum f. sp. lycopersici Fol and Tomato Mosaic Virus ToMV. Differentially expressed tomato genes upon inoculation with Fol and ToMV were identified at two days post-inoculation. A large overlap was found in differentially expressed genes throughout the two incompatible interactions. However, Gene Ontology enrichment analysis evidenced specific categories in both interactions. Response to ToMV seems more multifaceted, since more than 70 specific categories were enriched versus the 30 detected in Fol interaction. In particular, the virus stimulated the production of an invertase enzyme that is able to redirect the flux of carbohydrates, whereas Fol induced a homeostatic response to prevent the fungus from killing cells. Genomic mapping of transcripts suggested that specific genomic regions are involved in resistance response to pathogen. Coordinated machinery could play an important role in prompting the response, since 60% of pathogen receptor genes NB-ARC-LRR, RLP, RLK were differentially regulated during both interactions. Assessment of genomic gene expression patterns could help in building up models of mediated resistance responses.